Skeletal Diseases of the Growing Dog:

Skeletal development in the dog results from an interaction of
genetic, environmental, and nutritional factors. The genetic
component can be influenced when the populations are well
controlled, accurate breeding records are kept, and a desire to
improve the breed exists. Environmental factors such as housing and
activity level are under the owner's influence. Nutrition is one of the
single most important factors affecting development of the
musculoskeletal system, and energy, protein, and calcium are some
of the more critical nutritional components affecting skeletal
development. When given in excess, they can be detrimental to
normal skeletal growth.(1-7) Most pet owners in the United States
feed commercially prepared diets, which are balanced and complete.
The vast majority of developmental skeletal disorders diagnosed in
veterinary practice occur in large and giant breeds and are associated
with excess (i.e., inappropriate) intake of a commercial diet and/or
supplementation. The most prevalent developmental orthopedic
disorders are hip dysplasia and osteochondrosis.

CANINE HIP DYSPLASIA

Canine hip dysplasia (CHD) is the most frequently
encountered orthopedic disease in veterinary medicine practice. This
extremely common heritable disorder of the growing dog can be
influenced by nutrition. The period from 3 to 8 months of age
appears to be important in the development of CHD, with the first 6
months generally thought to be the most critical. Early
developmental findings of CHD, including joint laxity and
coxofemoral anatomic changes, have been documented within 2
weeks of birth. Rapid weight gain in German shepherds during the
first 60 days after birth has been associated with CHD at a later age.
Frequency and severity of CHD are influenced by weight gain in
growing dogs, especially if sired by parents with CHD or with a high
incidence of CHD in their offspring. Dogs with weight gains
exceeding breed standards have a higher frequency of CHD as well
as more severe CHD than dogs with weight gain below the standard
curve.(8)In one colony of fast growing Labrador retrievers, the
triradiate growth plates of the acetabula fused at 5 months as
determined by conventional radiography; normal closure of these
growth plates in pups growing at conventional rates has been
reported to occur at 6 months. Early fusion in the acetabulum is
speculated to result in bone/cartilage disparities in the future and to
predispose to dysplastic changes.(9) Limiting food intake in growing
Labrador retriever puppies has been associated with less subluxation
of the femoral head and fewer signs of hip dysplasia.(10)

OSTEOCHONDROSIS

Osteochondrosis (OCD) is a focal area of disruption in
endochondral ossification. OCD occurs in the physis and/or
epiphyseal regions of growth cartilage. This disease can be
generalized or systemic and is widespread among young, rapidly
growing, warm blooded, domesticated species and in humans. In all
species the etiology is considered multifactorial. In the dog, OCD
risk factors are associated with age, gender, breed, rapid growth, and
nutrient (primarily calcium) excesses.(1,11-14)

All large and giant breeds are at increased risk for OCD, with
Great Danes, Labrador retrievers, Newfoundlands, and rottweilers
having the highest risk.(14) Males have an increased risk of OCD in
the proximal humerus, but gender relationships are not found with
OCD involving other joints.(14)

Osteochondrosis lesions are routinely found in pigs as young
as 25 days of age.(15) These findings would help substantiate that
OCD may be caused by a localized, primary effect on the
chondrocyte rather than secondary effects of biomechanic force
because rapid growth and weight gain are much less of a factor at
this age. Regardless of the pathogenesis of OCD, the underlying role
of nutrition is still a factor. In the growing puppy, over nutrition can
result in a mismatch between body weight and skeletal growth,
which can lead to overloading of skeletal structures. Nutrition of the
mother may also play a role in the development of OCD in the
offspring.(16)

Although generalized nutrient excesses have been blamed for
OCD lesions, there is increasing evidence implicating specific
nutrients. Excessive calcium intake resulting in a hypercalcitoninism
and hypoparathyroidism(2) manifests as retarded bone maturation,
inhibition of osteoclastic activity, and slowed cartilage maturation.
These effects on bone and cartilage increase the incidence of
osteochondral lesions in articular and physeal cartilage.(2)
Osteochondrosis of the acetabular rim has been proposed to lead to a
shallow acetabulum and subsequent CHD in the dog. Most of the
studies evaluating the effect of vitamin C on OCD have used the pig
as a research model and agree that vitamin C supplementation has no
effect on the incidence of OCD.(8,17)

OVERNUTRITION

Overnutrition intended to maximize growth rate is
incompatible with optimal skeletal development in many species. An
early study suggesting a role of overnutrition in the development of
skeletal disease in dogs was that of Hedhammer and colleagues in
1974(1); in an effort to study the influence of food consumption on
the incidence of skeletal disease, these researchers performed an
experiment comparing ad libitum versus restricted dietary intake in
Great Dane puppies. The resultant skeletal pathology was markedly
increased in the ad libitum group. This study heightened the
awareness of the critical role nutrition plays in bone development.

NUTRIENTS AND SKELETAL DISEASE

Energy

Energy (calories) is needed for normal development;
however, needs vary based on breed, age, neuter status, and activity
level. Energy is essential for growth (osteoid formation) and
remodeling (resorption) of bone. A variety of methods are advocated
to determine energy requirements, and, consequently, estimates of
correct energy intake vary.(18) In general, growth requires twice the
energy needs of maintenance. As the dog approaches adult body
weight, energy needs decrease and are arbitrarily reduced to 1.6 times
maintenance energy requirements when the dog reaches 40% of adult
body weight.

Rapid velocity of growth in large and giant breeds increases
their risk of skeletal disease.(7,13) Excess energy per se in an
otherwise balanced diet is not a direct contributor to skeletal disease
in the growing dog(8,19); the link appears to occur when energy
contributes to rapid growth rates and excessive body weight.

Differences in energy requirements may exist within breeds
as well as among individuals. Newfoundlands and huskies may
require less energy for growth whereas Great Danes have a greater
than average growth energy requirement.(20) Although energy
calculation estimates still provide an excellent reference point, they
must be modified according to nutritional condition and level of
physical activity.

No statistically significant effect has been seen on the
incidence of CHD when a primarily carbohydrate energy source was
included or excluded from an otherwise nutritionally adequate diet.
Hip joint laxity, thought to be a predictor of CHD, does not seem to
be influenced directly by dietary energy. Increased growth rate on a
high-calorie diet stresses the tight hip and creates the potential for
increased laxity around the joint and subsequent changes consistent
with hip dysplasia. Similarly, an incongruent hip in a rapidly
growing, overweight puppy may not mature with the musculature.
Other than reduction of overall food consumption by restricting
intake, dietary energy has minimal or no influence on the production
or prevention of CHD.

Protein

Like excess energy, protein has been thought to be associated
with skeletal disease. A study by Nap and coworkers reported on the
role of protein in disturbances of skeletal development(21,22): Three
groups of Great Dane puppies were fed three levels of protein
(31.6%, 23.1%, and 14.6% on a dry matter basis) in an isoenergetic
dry dog food from 7 weeks through 18 weeks of age. No
demonstrable effects were noted on calcium metabolism or skeletal
development. These levels of dietary protein are unlikely to cause a
disturbing role in canine endochondral ossification.

Investigators have felt they were able to produce normal hip
growth and reduce CHD in mixed-breed puppies by feeding a high-
or all-meat diet. Subsequent studies in purebred animals known to be
dysplastic (German shepherds, golden retrievers, and Labrador
retrievers) and in female beagles have not shown similar results.(8)
High protein intake does not appear important for development of
normal hip joints.

While not directly responsible for skeletal disease in the
growing dog, protein provided in excess of metabolic requirements
is deaminated by the liver and used for energy, increases plasma
levels of insulin-like growth factors, and contributes to an increased
rate of growth.(23) If requirements for essential amino acids are met,
there are no known benefits to feeding excess protein to healthy,
young, growing dogs.

The minimum level of protein in a diet depends on
digestibility, amino acid composition, proper ratios among the
essential amino acids, and amino acid bioavailability from the protein
source. Energy density of the food and the physiologic state of the
dog play a role as well. A growth diet should contain more than 28%
protein (dry matter basis) of high biologic value that supplies at least
16% of the dietary energy. In the normal dog, dietary protein
requirements decrease with age.

Calcium

Plasma calcium concentration is tightly regulated by the
body. This regulation is needed for the many calcium-dependent
biologic processes, such as muscle contraction, hormonal release,
and blood coagulation. The release of calcium-regulating hormones
(parathyroid hormone [PTH], calcitonin [CT], and 1,25-
dihydroxycholecalciferol [1,25 vitamin D]) is influenced by plasma
calcium concentration. These hormones regulate calcium dynamics
in the intestine, kidneys, and bone.

Calcium excess is routed primarily to bone through the
influence of the calciotropic hormones on target organs. Chronic,
high intake of calcium in large breeds has been associated with
hypercalcemia, concomitant hypophosphatemia, rise in serum
alkaline phosphatase, retarded bone maturation, higher percentage of
total bone volume, retarded bone remodeling, decrease in osteoclasts,
and retarded maturation of cartilage. These changes cause
disturbances in endochondral ossification (articular and
epiphyseal).(6) When high calcium intake (calcium excess) is
coupled with relatively little absorption from bone, severe pathologic
changes occur in the young, growing skeleton that is unable to
respond by normal remodeling and endochondral ossification. The
clinical diseases associated with these changes are osteochondrosis,
retained cartilage cones, radius curvus syndrome, and stunted
growth.(1,6) Therefore, calcium excess is a major causative or
contributing factor in the pathogenesis of skeletal disease in the
growing giant-breed dog.(3-6)

It is the absolute level of calcium, rather than the
calcium/phosphorus ratio, that most influences skeletal disease.(11)
Young, giant-breed dogs fed a diet containing 3.3% calcium (dry
matter basis) and 0.9% or 3% phosphorus have significantly
increased incidence of developmental bone disease. These dogs seem
to be unable to protect themselves against the negative effects of
chronic excess levels of calcium.(26) Calcium levels for a growth
diet should be between 1% and 1.6% (dry matter basis). Often
puppies are switched from growth to maintenance diets to avoid
calcium excess and skeletal disease. However, because maintenance
diets are generally of much lower energy density than growth diets,
the puppy must consume more dry matter volume to meet its energy
requirement. If the calcium levels (dry matter basis) are similar
between the two diets, the puppy will actually consume more
calcium on the maintenance diet. This is exemplified in the case of
switching a 13-week-old Great Dane puppy from a typical growth
diet (4.2 kcal/g and 1.6% calcium on a dry matter basis) to a typical
maintenance diet (3.2 kcal/g and 1.4% calcium on a dry matter
basis). The puppy would consume approximately 638 g of the
growth diet containing 10.2 g calcium. To meet energy needs of
2680 kcal/day, this same puppy would consume approximately 838
g of the maintenance diet containing 11.7 g of calcium.

Feeding treats containing calcium or providing calcium
supplements further increases daily calcium intake. If the same 13-
week-old, 20 kg Great Dane puppy were given two level teaspoons
of a typical calcium supplement (calcium carbonate) in addition to the
growth diet, it would more than double its daily calcium intake. This
level is well beyond that shown to increase the risk for
developmental bone disease.(11)

Recent investigations produced osteochondrosis in the fetuses
of ewes fed high levels of dietary calcium.(24) Because of the rapid
growth rate of giant-breed dogs, they become "sentinels" for
nutritionally influenced skeletal disease such as is seen with excesses
in dietary calcium. Similar changes may be slower to surface and are
not as easily identified in the smaller breeds. Regardless of the risks
of high calcium intake, dietary calcium is a highly influential nutrient
for skeletal development.

Vitamin C

L-Ascorbic acid (vitamin C) is integral to hydroxylation of
proline and Iysine during biosynthesis of collagen. Type I collagen is
the most widely distributed in connective tissue (primarily in bone
and ligaments). In puppies fed diets devoid of vitamin C for 147 to
154 days, growth was not affected and skeletal lesions were not
noted.(25) There are no dietary requirements for vitamin C in the
dog.(25)

Vitamin C supplementation in pigs has produced elevations
in plasma levels; however, articular concentrations of hydroxyproline
were unchanged. Similar studies in dogs demonstrated transient
elevation of plasma vitamin C concentrations, and long-term
supplementation did not increase concentrations much above
normal.(8) Excess vitamin C supplementation is generally
considered to have little or no effect on the skeleton. The relationship
between vitamin C and developmental disorders of the skeletal
system in the dog is as yet unproven.

Megadoses of ascorbate fed to the bitch during pregnancy
and provided to the offspring until young adulthood have been
reported to eliminate CHD.(26) Ascorbate therapy was rationalized
as an antistressor, a detoxicant, a metabolite necessary for
maintaining biochemical homeostasis in the body, and a component
in collagen synthesis. Eight litters of German shepherd puppies from
known dysplastic parents or from parents that had produced
dysplastic offspring were studied. The bitch received 2 to 4 g sodium
ascorbate crystals per day during pregnancy. The puppies received
calcium and vitamin supplements from birth to 3 weeks, 500 mg
ascorbate per day from 3 weeks to 4 months, and I to 2 g ascorbate
per day from 4 months up to 2 years. No CHD was reported in any
of the offspring. However, no radiographs were taken to document
presence or absence of dysplastic changes, and no long-term follow-
up studies have been published. Neither this nor any other study has
verified ascorbic acid levels, much less deficiencies, in dogs with hip
dysplasia.(8) If CHD were to be associated with a low vitamin C
level, lower concentrations would be more likely in younger animals
undergoing the stresses of growth. No other studies have
demonstrated a positive effect of oral supplementation of vitamin C
in preventing CHD in growing dogs that are genetically at risk for the
disease. Decreased levels of hydroxyproline found in arthritic
cartilage from CHD joints are probably a reflection of degradation
changes rather than lack of production .

Finally, the relationship between vitamin C, joint laxity, and
CHD in the dog is suspect because a decrease in systemic vitamin C
levels could be expected to affect other joints. Canine hip dysplasia is
often associated with degenerative disease in multiple joints;
however, joint laxity other than in the hips is not reported.

Electrolyte Balance

Dietary electrolytes have been proposed as a preventative for
CHD.(27,28) The dietary anion gap (DAG) was associated with the
radiographic changes of subluxation in the coxofemoral joints of
several breeds. The basic premise is the anions and cations
(specifically Na+, K+, and Cl ) in the diet influence the electrolytes
and osmolality in the joint fluid. Higher osmolality and increased
fluid volume have been noted in the joint fluid of dysplastic dogs
when contrasted to disease-free hips in the same breed.(28) The
observed changes in osmolality and volume could be a result rather
than a cause of CHD. A DAG of (Na+ + K+ Cl ) <23 mEq/100 g of
food was fed to large-breed dogs and resulted in less femoral head
subluxation, on average, at 6 months of age. This beneficial effect
was also thought to be maintained at 2 years of age. The effect
(slowed progression of subluxation) was also observed in dogs fed
lower DAG from 33 to 45 weeks of age.(28) However, changes in
synovial fluid osmolality and electrolyte concentrations were not
reported. Hip joint laxity was determined using the Norberg hip
score computed from radiographs. Significant correlation between
radiographic findings (e.g., Norberg hip scores) and progression of
CHD, either radiographically or clinically, is not proven. The studies
suggesting an association between DAG and joint laxity did not
prove a mechanism of action.

Other Nutrients

Vitamin D metabolites are important in the regulation of
calcium metabolism and, subsequently, skeletal development in
dogs. They aid in the absorption of calcium and phosphate, increase
bone cell activity, and influence endochondral ossification and
calcium excretion.(29) Unlike other omnivores, the dog seems to be
dependent on dietary vitamin D sources. Dietary sources of vitamin
D are either of plant (vitamin D2) or animal (vitamin D3) origin.
Commercial pet foods contain from 2 to 10 times the National
Research Council (NRC) recommended amounts of vitamin D.(30)
Clinical cases of vitamin D deficiency (rickets) are extremely rare.
Diagnosis of a deficiency can be made by measuring circulating
levels of vitamin D metabolites(31) and by measuring growth plate
width. Increased width is not associated with low-calcium/high-
phosphate diets but is a strong indicator of rickets.(29) Excess
vitamin D can cause hypercalcemia, hyperphosphatemia, anorexia,
polydipsia, polyuria, vomiting, muscle weakness, generalized soft
tissue mineralization, and lameness. In the growing dog,
supplementation with vitamin D can result in marked disturbance of
normal skeletal development, primarily as a result of increased
calcium and phosphate absorption.(29)

The trace mineral elements copper and zinc have been
implicated in normal skeletal development. Supplementing a mare's
dietary copper intake during the late stages of pregnancy and
supplementing the foal's diet from 90 to 180 days of age have been
associated with a reduced prevalence and severity of developmental
cartilage lesions.(32) Copper deficiency in the dog has been
associated with hair depigmentation, hyperextension of the distal
phalanges, and tissue copper decreases in the hair, liver, kidney, and
heart muscle. However, copper concentration in bone was not
influenced by dietary treatment, and developmental skeletal
abnormalities associated with a deficiency of dietary copper were not
described.(33) Similarly, long-term studies of dietary zinc levels on
canine growth and reproduction showed no significant clinical
influence on skeletal development.(34)

CONCLUSION

The large and giant breeds are the most susceptible to skeletal
disease. Genetics, environment, and nutrition play key roles.
Nutritionally, rate of growth, feed consumption, specific nutrients,
and feeding methods influence our ability to optimize skeletal
development and minimize skeletal disease. Maximizing the growth
rate in young, growing puppies does not correlate to maximal adult
size; however, it does increase the risk of skeletal disease. The
growth phase of 3 to 8 months and possibly the phase prior to
weaning are integral to ultimate skeletal integrity. The giant breeds
may be limited in their ability to cope with excesses of minerals such
as calcium, and the results are abnormal bone remodeling and
skeletal disorders. This apparent increased sensitivity makes these
breeds somewhat of a monitor of dietary influences.

Nutritional management alone will not be sufficient to
manage developmental bone diseases. However, we can prevent
some skeletal disease by appropriately feeding diets with optimized
nutrients. Dietary deficiencies are of minimal concern in this age of
commercial diets that are specifically prepared for young, growing
dogs. The potential for harm is in overnutrition from excess
consumption and supplementation.